K. Sue O'Shea received a Ph.D. in 1979 from the University of Cambridge, England, and is currently an Assistant Professor of Anatomy and Cell Biology at the University of Michigan. Her research has examined the early events involved in neurulation and more recently the role of the extracellular matrix in the development of the nervous system. The goals of this application are to provide salary support via a research career development award to allow her to devote essentially full time to bench research. The goal of this intensive research effort will be to extend the current cellular and developmental biology strengths of the lab to an approach based more heavily on molecular biology technologies. During the tenure of a career development award, the Department of Anatomy and Cell Biology will increase the time and resources available for the research. Specifically, Dr. O'Shea will be relieved of the majority of her teaching responsibilities, her space will be significantly upgraded, and "salary savings" will be returned to her to hire a postdoctoral research associate or technician. The excellent resources at the University of Michigan, in combination with increased time for bench work should both expedite the proposed research and significantly advance Dr. O'Shea's research career. The specific goals of the research are an expanded version of her R01, which addresses fundamental cell biological questions of the response of developing astroglia and granule cell neurons to a unique extracellular matrix protein, thrombospondin (TSP). Recently, a second thrombospondin gene has been identified which is expressed at high levels in the developing CNS. Adhesion, process outgrowth, and motility will be examined for TSP1 and TSP2, using as a model "purified" astroglial and granule cell neurons from the developing cerebellar cortex. These studies will be expanded to include experiments aimed at determining the role of TSP1 and 2 in neuron - glial cell interactions using recently developed lines of C6 glioma cells stably transfected to alter their expression of cell surface TSPs. The proposed research should elucidate the role of a unique extracellular matrix component in the early development of the nervous system; support via an RCDA will expedite this specific line of research, and provide valuable resources and time for Dr. O'Shea to focus on the work and bring more powerful techniques into the laboratory.